Hypnotic and analgesic compound



Patented Aug. 4, 1942 2,292,264 HYPNOTIC AND ANALcnsIc COMPOUND Meyer L. Axelrod, Detroit, Mich.

No Drawing. Application April 1, 1939, Serial No. 265,598

11 Claims.

' This invention relates to improvements in hypnotic compounds such as analgesics and anaesthetics. In my prior Patent No. 1,928,346 of September 26, 1933, I discussed in detail the advantages of hypnotic compound for rectal instillation comprising a solution of oil, ether, and a barbiturate.

The present invention is adapted to fulfill a similar purpose to that of the aforesaid patent, the object being to provide a safe anaesthetic for rectal instillation.

Still another object of the invention is to provide a barbituric acid solution that is stable and will not break down throughout a period of time forming deleterious compounds.

Still another object of my invention is to provide a rectal anaesthetic wherein the volume of the compound is greatly reduced, thus reducing the tendency of the bowel to expel the same.

Still another object of the invention is to provide an analgesic compound for rectal instillation which has no irritating properties and which is not too depressing to the patient.

Still other objects and uses of the compound will become apparent from the following description of the method of compounding and the use thereof.

Broadly the invention comprises using a concentrated solution of any barbituric acid in tertiary amyl alcohol, commonly known as amylene hydrate. This solution, having both analgesic and hypnotic properties, is injected rectally, whereupon its efiects are realized in a relatively short time.

Furthermore, although the amylene hydrate has some slight analgesic properties, they'are too weak to be of any value. Combining the amylene hydrate with a barbituric acid, causes the two to act synergistically to give quick analgesia over a relatively long period. This period is not only quicker than could be expected from the use of any one alone, but is considerably longer in duration than would ordinarily be expected due to the synergistic action. That is, amylene hydrate has practically no hypnotic properties and very little analgesic properties, the barbituric acids have little analgesic value and a delayed hypnotic action, combined, the two compounds provide a quick and long analgesic and hypnotic action which is much greater than as if the results of using the compounds were merely additive.

A dose suitable for providing analgesia in the ordinary obstetrical case may comprise -15 grains of barbituric acid, 4-5 cc. of amylene hydrate, with 30 cc. of oil to give it body for instillation.

The amount of barbituric acid may vary within certain ranges depending upon the kind used, but I have found that 10 grains of cyclo-pentenylallyl barbituric acid to be very eflicacious. Furthermore, the amount of oil may be considerably less, reducing the volumeof the material. Obviously, the smaller amount of material is more easily retained. The amount of dosage may also be varied according to the body weight of the patient, large patients requiring a slightly larger dose and small patients, less.

Heretofore, barbituric acid solutions were relatively unstable, breaking down into compounds which were ineffective and injurious to the system. Barbituric acids in amylene hydrate are very stable and may be kept for long periods of time without any danger of breaking down into subsidiary compounds, which might be dangerous.

Furthermore, the small amount of amylene hydrate necessary to place the barbituric acid into solution, is of a distinct advantage, since it permits a small bulk of material to be introduced rectally, lessening or entirely eliminating any tendency for the same to be expelled.

Another distinct advantage resides in the fact that, should the preliminary cleaning of the bowel not have removed all the fecal matter, the amylene hydrate permits action even in the presence of such fecal matter. This, of course, is not true where barbiturates are used in water solution or in the form of suppositories.

Although the cyclo-pentenyl-allyl' barbituric acid has been stated as one of the preferred forms, the other barbituric acids are effective and may be substituted with good results; for instance, iso-amyl-ethyl barbituric acid; diallyl barbituric acid; n-butyl-ethyl barbituric acid; allyl-isopropyl barbituric acid; ethyl-l-methyl butyl barbituric acid; ethyl-isopropyl barbituric acid, cyclo-hexenyl-ethyl barbituric acid or isoamyl-ethyl barbituric acid, may be used.

A master solution may be prepared proportioned according to the above, and will be found to have excellent keeping qualities.

In preparing the solution, 10 grains of a barbituric acid may be dissolved to each 4 cc. of amylenehydrate to form the master solution.

Dosage for the patient is determined according to body weight and the barbituric acid which 'is used in solution, there usually being 1 grain of barbituric acid used for each 15 pounds of body weight. For instance, a patient weighing pounds would require 9 grains of the barbiturate,

in bulk. The amylene hydrate and the barbituric acid are definitely synergistic or co-active in their action, the combined action simulating a condition similar to that as when a mild opiate is administered with barbituric acid. When the barbiturate alone is used a certain definite period of analgesia per grain of barbiturate can be expected, depending upon the body weight of the patient. Also amylene hydrate has a certain definite eflect in a similar manner. However, when the two are combined I have found that due to the synergy or coaction between the two chemicals, the analgesia period is continued for a definitely longer time than would be expected if the results of the addition of the two chemicals or drugs was merely additive.

The instillation of the foregoing compound is accomplished in obstetrical cases by first giving enemas to the patient until the return is clear. The mixture is then instilled, .the small volume permitting a rapid instillation. The amylene hydrate in itself, if used alone, is too weak to be of value in surgical or obstetrical cases. barbiturate used alone has a tendency to cause restlessness; however, when the two are combined as described, a considerable period of analgesia is had, permitting the material to be administered during the first stages of labor and maintaining analgesia for sufiicient duration of time to permit the patient considerable rest after labor is completed.

It is not my intention that the invention should be limited to the exact proportions described in the specifications since it is obvious The' to those skilled in the art that variations in volumetric contents may be made and that other variations may be made, but without departing from the scope of the invention.

I claim: i

1. A hypnotic compound for rectal instillation comprising a solution of a barbituric acid efiective in anaesthesia and amylene hydrate.

2. A hypnotic compound for rectal instillation comprising a solution of a. barbituric acid effective in anaesthesia and amylene hydrate and ofl.

3. A hypnotic compound for rectal instillation comprising 10 grains of a barbituric acid effective in anaesthesia dissolved in 4 cc. of amylene hydrate.

4. A hypnotic compound for rectal instillation comprising a solution of a barbituric acid effective in anaesthesia, amylene hydrate and water.

5. A hypnotic compound for rectal instillation comprising 10 grains of a barbituric acid effective in anaesthesia, 4 cc. amylene hydrate, and 1 ounces of oil.

6. A hypnotic compound for rectal instillation comprising a solution of cyclo-pentenyl-allyl barbituric acid and tertiary-amyl-alcohol.

7. A hypnotic compound for rectal instillation comprising 10 grains of cyclo-pentenyl-allyl barbituric acid, 4 cc. of tertiary-amyl alcohol and oil for increasing the bulk.

8. A hypnotic compound for rectal instillation comprising a solution of ethyl-l-methyl butyl barbituric acid and tertiary-amyl-alcohol.

9. A hypnotic compound for rectal instillation comprising 10 grains of ethyl-l-methylbutyl barbituric acid, 4 cc. of tertiary-amyl alcohol and oil for increasing the bulk.

10. A hypnotic compound for rectal instillation comprising a solution of allyl-iso-propyl barbituric acid and tertiary-amyl-alcohol.

11. A hypnotic compound for rectal instillation comprising allyl-iso-propyl barbituric acid, 4 cc. of tertiary-amyl alcohol and oil for increasing the bulk.

MEYER L. AXELROD. 

